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EMBO Practical Course: Bioinformatics and Genome Analysis, 5–17 June 2017.


art + science activism

Watch the video of this project, which features the participants who have a BRCA mutation and their interaction with the piece. The video also highlights the design and construction of the mural.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Science and art and personal stories of cancer survivors combine into this beautiful depiction of the complexity and individuality of the genome. (Free the Data)

Human Genome Art by Humans with Genomes

I recently took part in a deeply meaningful collaboration of science, art and personal stories of cancer survivors.

Together with Joanna Rudnick and Aaron De La Cruz, we sought to create a work of art that combines the science of cancer genomics and the individuals whose lives are affected by genetic mutations in the BRCA1 and BRCA2 genes, where genomic changes drastically increase one's chances of breast and ovarian cancer.

We wanted to make something that is scientifically accurate, artistically beautiful and emotionally engaging. The complexity of the genome, the multitudes of other genes and possible mutations and the millions of personal stories of hardship and survival were just a few of the elements we wanted to include the the piece.

My role was to provide the scientific direction behind the design and incorporate it into the aesthetic of Aaron De La Cruz, a street artist from San Francisco whose work echoes information, complexity, interaction and continuity. We all have a genome — a different genome. The ways in which our genomes are different is what gives us traits like hair and eye color, but is also what makes some of us predisposed to diseases like cancer.

The mural, which includes elements drawn by the cancer survivors, is part of the Free the Data campaign, which is advocating for an open access model of genome mutation databases so that scientists everywhere can analyze it and help women make informed choices about their breast-cancer risk.

The piece Importance of Data Sharing by Nature Methods illustrated the point:

Imagine you are a physician or researcher and seek to get more confirmation on the clinical impact of particular genetic variants. If your search of public databases comes up empty this does not necessarily mean that nothing is known about the mutations in question. Rather, the information may be locked away as a trade secret in a genetic testing company’s proprietary database.

The New York Times article DNA Project Aims to Make Public a Company’s Data on Cancer Genes captures the current state of the situation.

The mural was constructed on location at InVitae in San Francisco.

A video of the project is available.

Beautiful, meaningful and personal

This work will be, as far as I know, the first human annotation of mutations in the human genome by humans whose genomes have the mutations. That's quite a term!

I've always been mindful of the necessity of the mingling of art and science. In my work I tried to add things I felt about the science I thought to create work that combines our objective understanding of the world we live in with the subjective experience of living in it. This project, by far, has been the most keenly felt.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Adding emotion, keeping the science. (Free the Data)

the design

The mural was created in San Francisco on Saturday, July 13th, 2013. We are starting with a 11' x 6' wood canvas. These dimensions reflect the ratio of lengths of BRCA1 and BRCA2 proteins (1,863 and 3,418 amino acids, respectively)

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The canvas aspect ratio reflects the ratio of BRCA1 and BRCA2 protein lengths. The proteins are represented on the canvas as lines. (Free the Data)

The BRCA1 and BRCA2 proteins are drawn on the canvas as straight-line sections.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The genes are depicted on the canvas as their protein products. (Free the Data)

The locations of the participants mutations are positioned on the protein lines as circles. For individuals with large deletions, the circle is placed at the first affected amino acid. Because BRCA1 is location on the opposite strand (anti-sense), its start on the canvas is on the right.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
11 mutations, one for each of the cancer previvor and survivor participants, are placed on the protein lines as circles. The start of BRCA1 is on the right to reflect that this gene is on the anti-sense strand. (Free the Data)

The rest of the genome is now drawn. Aaron's style is perfect for depicting information and the endless complexity of the genome and its interacting elements. We were careful to include elements that indicate that the story told today is not complete. Millions of others have mutations in thousands of other genes, each potentially life-threatening. Just as the stories of our participants will continue to evolve, other stories are waiting to be told.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
BRCA1 and BRCA2 proteins and their mutations, together with the rest of the genome. Other lines and circles hint at other genes, other mutations, as well as the biochemical interactions in the cells and personal interactions of those affected by the mutations. (Free the Data)

Once the "reference" genome is depicted, participants with BRCA1 and BRCA2 mutations will complete the art work by individually marking the positions of their mutations on the art using personalized colors. With Aaron's help, everyone created their own color by mixing primary colors.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Participants fill in their mutation circles with their personalized color. (Free the Data)

From base pair, to genome, to person, to life. All it takes is one tiny change in the genome to change a life forever.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The mutations of 11 people in the vastness of the genome. What's your story? (Free the Data)

creation of free the data mural

The BRCA1 and BRCA2 lines were placed on the canvas by first pinning two pieces of string, marked with the positions of the mutations.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
String was used to mark the placing of lines and mutations. (Free the Data)

After drawing the protein lines, it was time to fill the canvas.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Aaron De La Cruz creating the art work. Here, he is filling the space in the canvas around the BRCA1 and BRCA2 segments with his design. The project was shot with a Red Camera—this is a sequence from its render application. (Free the Data)

Over the next 4 hours, Aaron filled in the canvas with the "rest" of the genome.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Aaron De La Cruz creating the art work. Here, he is filling the space in the canvas around the BRCA1 and BRCA2 segments with his design. The project was shot with a Red Camera—this is a sequence from its render application. (Free the Data)

Participants

Lucy, Karen, Steve, Ghecemy, Joanna, Jill, Lisa, Lynn, Ruth, Jenica, Susan

Cancer previvors and survivors who have been diagnosed with a mutation on BRCA1 or BRCA2 genes.

Joanna Rudnick (director/producer)

Joanna made her directorial debut with the Emmy-nominated In the Family, a deeply personal film about coming to terms with testing positive for the breast cancer gene BRCA1 mutation and following the storylines of other women and families facing the same hard choices. In the Family premiered at Silverdocs in 2008, was broadcast nationally on PBS P.O.V. the same year and was a finalist for the NIHCM Foundation’s Health Care Radio and Television Journalism Award.

Joanna received a master’s degree in Science and Environmental Journalism from New York University and a bachelor’s degree in English from Northwestern University. Joanna loves the opportunity to teach and mentor and served as an adjunct professor at Northwestern University’s Medill School of Journalism in the past.

She has written for several publications including Audubon Magazine, The Artful Mind, The Berkshire Record and Humanities. Before finding her way to the wonderful world of documentaries, Joanna served as an Americorps volunteer, implementing project-based environmental curricula in the San Francisco Public School System.

Joanna is one of the cancer survivors whose mutations are encoded in the art.

http://kartemquin.com/about/joanna-rudnick

Aaron De La Cruz (artist)

Aaron De La Cruz's work, though minimal and direct at first, tends to overcome barriers of separation and freely steps in and out of the realms of design, graffiti, and illustration.

The parameters he has chosen to work within actually allow him to free himself and react to the very limitations he has created. This overriding structure and the lack of deliberation while moving within creates a tension when encountering his work due to the almost computer generated grid like systems he creates by unplanned markmaking. The act and the marks themselves are very primal in nature but tend to take on distinct and sometimes higher meanings in the broad range of mediums and contexts they appear in and on.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Work by Aaron De La Cruz. (Aaron De La Cruz)

His work finds strengths in the reduction of his interests in life to minimal information. De La Cruz gains from the idea of exclusion, just because you don't literally see it doesn't mean that its not there.

http://www.aarondelacruz.com

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news + thoughts

Classification and regression trees

Fri 28-07-2017
Decision trees are a powerful but simple prediction method.

Decision trees classify data by splitting it along the predictor axes into partitions with homogeneous values of the dependent variable. Unlike logistic or linear regression, CART does not develop a prediction equation. Instead, data are predicted by a series of binary decisions based on the boundaries of the splits. Decision trees are very effective and the resulting rules are readily interpreted.

Trees can be built using different metrics that measure how well the splits divide up the data classes: Gini index, entropy or misclassification error.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Classification and decision trees. (read)

When the predictor variable is quantitative and not categorical, regression trees are used. Here, the data are still split but now the predictor variable is estimated by the average within the split boundaries. Tree growth can be controlled using the complexity parameter, a measure of the relative improvement of each new split.

Individual trees can be very sensitive to minor changes in the data and even better prediction can be achieved by exploiting this variability. Using ensemble methods, we can grow multiple trees from the same data.

Krzywinski, M. & Altman, N. (2017) Points of Significance: Classification and regression trees. Nature Methods 14:757–758.

Background reading

Lever, J., Krzywinski, M. & Altman, N. (2016) Points of Significance: Logistic regression. Nature Methods 13:541-542.

Altman, N. & Krzywinski, M. (2015) Points of Significance: Multiple Linear Regression Nature Methods 12:1103-1104.

Lever, J., Krzywinski, M. & Altman, N. (2016) Points of Significance: Classifier evaluation. Nature Methods 13:603-604.

Lever, J., Krzywinski, M. & Altman, N. (2016) Points of Significance: Model Selection and Overfitting. Nature Methods 13:703-704.

Lever, J., Krzywinski, M. & Altman, N. (2016) Points of Significance: Regularization. Nature Methods 13:803-804.

...more about the Points of Significance column

Personal Oncogenomics Program 5 Year Anniversary Art

Wed 26-07-2017

The artwork was created in collaboration with my colleagues at the Genome Sciences Center to celebrate the 5 year anniversary of the Personalized Oncogenomics Program (POG).

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
5 Years of Personalized Oncogenomics Program at Canada's Michael Smith Genome Sciences Centre. The poster shows 545 cancer cases. (left) Cases ordered chronologically by case number. (right) Cases grouped by diagnosis (tissue type) and then by similarity within group.

The Personal Oncogenomics Program (POG) is a collaborative research study including many BC Cancer Agency oncologists, pathologists and other clinicians along with Canada's Michael Smith Genome Sciences Centre with support from BC Cancer Foundation.

The aim of the program is to sequence, analyze and compare the genome of each patient's cancer—the entire DNA and RNA inside tumor cells— in order to understand what is enabling it to identify less toxic and more effective treatment options.

Principal component analysis

Thu 06-07-2017
PCA helps you interpret your data, but it will not always find the important patterns.

Principal component analysis (PCA) simplifies the complexity in high-dimensional data by reducing its number of dimensions.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Principal component analysis. (read)

To retain trend and patterns in the reduced representation, PCA finds linear combinations of canonical dimensions that maximize the variance of the projection of the data.

PCA is helpful in visualizing high-dimensional data and scatter plots based on 2-dimensional PCA can reveal clusters.

Altman, N. & Krzywinski, M. (2017) Points of Significance: Principal component analysis. Nature Methods 14:641–642.

Background reading

Altman, N. & Krzywinski, M. (2017) Points of Significance: Clustering. Nature Methods 14:545–546.

...more about the Points of Significance column

`k` index: a weightlighting and Crossfit performance measure

Wed 07-06-2017

Similar to the `h` index in publishing, the `k` index is a measure of fitness performance.

To achieve a `k` index for a movement you must perform `k` unbroken reps at `k`% 1RM.

The expected value for the `k` index is probably somewhere in the range of `k = 26` to `k=35`, with higher values progressively more difficult to achieve.

In my `k` index introduction article I provide detailed explanation, rep scheme table and WOD example.

Dark Matter of the English Language—the unwords

Wed 07-06-2017

I've applied the char-rnn recurrent neural network to generate new words, names of drugs and countries.

The effect is intriguing and facetious—yes, those are real words.

But these are not: necronology, abobionalism, gabdologist, and nonerify.

These places only exist in the mind: Conchar and Pobacia, Hzuuland, New Kain, Rabibus and Megee Islands, Sentip and Sitina, Sinistan and Urzenia.

And these are the imaginary afflictions of the imagination: ictophobia, myconomascophobia, and talmatomania.

And these, of the body: ophalosis, icabulosis, mediatopathy and bellotalgia.

Want to name your baby? Or someone else's baby? Try Ginavietta Xilly Anganelel or Ferandulde Hommanloco Kictortick.

When taking new therapeutics, never mix salivac and labromine. And don't forget that abadarone is best taken on an empty stomach.

And nothing increases the chance of getting that grant funded than proposing the study of a new –ome! We really need someone to looking into the femome and manome.